Transcription factor Nrf2 plays a pivotal role in protection against elastase-induced pulmonary inflammation and emphysema
Open accessAbstract
Emphysema is one of the major pathological abnormalities associated with chronic obstructive pulmonary disease. The protease/antiprotease imbalance and inflammation resulting from oxidative stress have been attributed to the pathogenesis of emphysema. Nrf2 is believed to protect against oxidative tissue damage through the transcriptional activation of a battery of antioxidant enzymes. In this study, we investigated the protective role of Nrf2 in the development of emphysema using elastase-induced emphysema as our model system. We found that elastase-provoked emphysema was markedly exacerbated in Nrf2-knockout (KO) mice compared with wild-type mice. The severity of emphysema in Nrf2-KO mice correlated intimately with the degree of lung inflammation in the initial stage of elastase treatment. The highly inducible expression of antioxidant and antiprotease genes observed in wild-type alveolar macrophages was significantly attenuated in the lungs of Nrf2-KO mice. Interestingly, transplantation of wild-type bone marrow cells into Nrf2-KO mice retarded the development of initial lung inflammation and subsequent emphysema, and this improvement correlated well with the appearance of macrophages expressing Nrf2-regulated antiprotease and antioxidant genes. Thus, Nrf2 appears to exert its protective effects through the transcriptional activation of antiprotease and antioxidant genes in alveolar macrophages.
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Tissue and plasma from Nrf2KO mice present higher levels of inflammation at 4 months of age.
“Our data show that tissue and plasma from Nrf2KO mice present higher levels of inflammation at 4 month of age (measured by the cytokine levels), corroborating previous reports (Ishii et al., 2005; Khor et al., 2008).”
From Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism (2017) · cites this paper as Ishii et al., 2005
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- Authors
- Ishii, Y., Itoh, K., Morishima, Y., Kimura, T., Kiwamoto, T., IIzuka, T., Hegab, A. E., Hosoya, T., Nomura, A., Sakamoto, T., Yamamoto, M., & Sekizawa, K.
- Affiliations
- University of Tsukuba (JP)
- Department of Respiratory Medicine, University of Tsukuba , Tsukuba ,
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-11
- Volume
- 175
- Issue
- 10
- Pages
- 6968-6975
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1631169176
- Cited by
- 248
- References
- 39
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 12 · 2023: 5 · 2022: 10 · 2021: 13 · 2020: 20 · 2019: 12 · 2018: 16 · 2017: 10 · 2016: 13 · 2015: 10 · 2014: 12 · 2013: 17 · 2012: 14
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science and Technology Agency
- Exploratory Research for Advanced Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Keywords
- Nrf2, emphysema, elastase-induced lung injury, lung inflammation, alveolar macrophages, protease-antiprotease imbalance, oxidative stress, antioxidant genes, bone marrow transplantation, Nrf2 knockout mice, chronic obstructive pulmonary disease
- MeSH terms
- Animals, Antioxidants, Emphysema, Inflammation, Lung, Mice, Inbred BALB C, Pancreatic Elastase, Pneumonia, Protease Inhibitors, Gene Expression, Bone Marrow Transplantation, Mice, Knockout, NF-E2-Related Factor 2, Mice
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